Aspergillus fumigatus is the most common cause of life-threatening mold infection (aspergillosis). Its spores are found in the air everywhere and are therefore unavoidable. It particularly affects those with damaged immune systems, especially transplant recipients, those on corticosteroids and leukemia patients. Autopsy studies have shown a prevalence of invasive aspergillosis of 4% in University hospitals, a 1400% increase on one decade earlier. This application is for the US contribution to the genome sequencing of A. fumigatus through an international initiative led by the applicant. The international contributors are the US (Manchester/TIGR), the UK (Sanger), France (Genoscope), Spain and Japan. The genome is estimated to be 30Mb in size containing about 8000 genes. This proposal is to sequence and annotate 12Mb, about 40% of the genome. The project has been initiated at the Sanger with the construction and characterization of a 100Kb BAC library. This library will serve as the resource for the assignment of genomic regions to sequencing centres. Data release will be at least monthly. The seguencing and initial annotation will be completed within 3 years. The sequencing and informatics technology to be developed with this project at TIGR will extend whole genome sequencing by reducing costs and improving quality for small eucaryotic genomes. Additionally this project will serve as a model of international collaboration for medium-sized genomes. Progress of the project and sequence data will be brought together on the Aspergillus Website (www.aspergillus.man.ac.uk). The key benefit from this project will be a genetic resource, available for all time, to understand Aspergillus, including basic biological systems, virulence characteristics, key antigens for allergenicity and immune protection, mechanisms of drug resistance, new antifungal drug targets and secondary metabolite production. This unique resource will bring in the larger Aspergillus research community to translate much of what is known of other Aspergillus species (nidulans, flavus/parasiticus, niger) to develop tools for managing human disease and to develop a functional understanding of the entire physiology and metabolism of the organism.